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ISSN: 2146-832X (Print)
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Review Article

Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis

Ertan Altaylı, Ercan Malkoc, Bilal Fırat Alp, Ahmet Korkmaz.

Free radicals and non-radical reactive molecules as well as several cytokines (e.g. tumor necrosis factor-α and interleukin family) and transcription factors (e.g. nuclear factor-κB and activator protein-1) are now known to take part in the pathogenesis of cyclophosphamide (CP) and ifosfamide (IF) induced hemorrhagic cystitis (HC). When these molecular factors are taken into account pathogenesis of bladder toxicity can be summarized in three steps: (1) acrolein rapidly enters into the uroepithelial cells, (2) activates intracellular ROS and NO production (directly or through transcription factors) leading to peroxynitrite production, and (3) finally the elevated peroxynitrite level basically damages lipids (lipid peroxidation), proteins (protein oxidation) and DNA (strand breaks) leading to PARP activation, a DNA repair enzyme. DNA damage causes PARP overactivation, resulting in the depletion of oxidized nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP), and consequently in necrotic cell death.
There is no doubt that for an effective prevention against CP- and IF-cystitis all pathophysiological mechanisms must be taken into consideration. Experimental works reporting beneficial effects of antioxidants, iNOS inhibitors, cytokine blockers or hyperbaric oxygen (HBO) treatment, against CP- and/or IF-induced HC exist in literature. In this article, we discussed the possible mechanisms and effectiveness of agents used in addition to mesna to prevent CP- and IF-cystitis. In conclusion, antioxidants, iNOS inhibitors, peroxynitrite scavengers, anti-inflammatory agents, as well as HBO therapy may be added to mesna administration in clinical trials in order to obtain the best protocol to improve quality of patients comfort.

Key words: cyclophosphamide, ifosfamide, cystitis, mesna, antioxidants, hyperbaric oxygen

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How to Cite this Article
Pubmed Style

Altaylı E, Malkoc E, Alp BF, Korkmaz A. Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis. J Mol Pathophysiol. 2012; 1(1): 53-62. doi:10.5455/jmp.20120321060902

Web Style

Altaylı E, Malkoc E, Alp BF, Korkmaz A. Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis. [Access: February 28, 2015]. doi:10.5455/jmp.20120321060902

AMA (American Medical Association) Style

Altaylı E, Malkoc E, Alp BF, Korkmaz A. Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis. J Mol Pathophysiol. 2012; 1(1): 53-62. doi:10.5455/jmp.20120321060902

Vancouver/ICMJE Style

Altaylı E, Malkoc E, Alp BF, Korkmaz A. Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis. J Mol Pathophysiol. (2012), [cited February 28, 2015]; 1(1): 53-62. doi:10.5455/jmp.20120321060902

Harvard Style

Altaylı, E., Malkoc, E., Alp, B. F. & Korkmaz, A. (2012) Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis. J Mol Pathophysiol, 1 (1), 53-62. doi:10.5455/jmp.20120321060902

Turabian Style

Altaylı, Ertan, Ercan Malkoc, Bilal Fırat Alp, and Ahmet Korkmaz. 2012. Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis. Journal of Molecular Pathophysiology, 1 (1), 53-62. doi:10.5455/jmp.20120321060902

Chicago Style

Altaylı, Ertan, Ercan Malkoc, Bilal Fırat Alp, and Ahmet Korkmaz. "Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis." Journal of Molecular Pathophysiology 1 (2012), 53-62. doi:10.5455/jmp.20120321060902

MLA (The Modern Language Association) Style

Altaylı, Ertan, Ercan Malkoc, Bilal Fırat Alp, and Ahmet Korkmaz. "Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis." Journal of Molecular Pathophysiology 1.1 (2012), 53-62. Print. doi:10.5455/jmp.20120321060902

APA (American Psychological Association) Style

Altaylı, E., Malkoc, E., Alp, B. F. & Korkmaz, A. (2012) Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis. Journal of Molecular Pathophysiology, 1 (1), 53-62. doi:10.5455/jmp.20120321060902

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